CCDC65, encoding a component of the axonemal Nexin-Dynein regulatory complex, is required for sperm flagellum structure in humans

We report two unrelated patients showing multiple morphological abnormalities of the sperm flagella (MMAF) and carrying distinct homozygous truncating variants in the PCD-associated gene CCDC65. We characterized one of the identified variants (c.1208del; p.Asn403Ilefs*9), which induces the near absence of CCDC65 protein in patient sperm. In Chlamydomonas, CCDC65 ortholog (DRC2, FAP250) is a component of the Nexin-Dynein Regulatory complex (N-DRC), which interconnects microtubule doublets and coordinates dynein arms activity. In sperm cells from the patient, we also show the loss of GAS8, another component of the N-DRC, supporting a structural/functional link between the two proteins. Our work indicates that, similarly to ciliary axoneme, CCDC65 is required for sperm flagellum structure. Importantly, our work provides first evidence that mutations in the PCD-associated gene CCDC65 also cause asthenozoospermia.PMID:37975235 | DOI:10.1111/cge.14459

Source: Clinical Genetics - November 17, 2023 Category: Genetics & Stem Cells Authors: Fadwa Jreijiri Emma Cavarocchi Amir Amiri-Yekta Caroline Cazin Seyedeh-Hanieh Hosseini Elma El Khouri Catherine Patrat Nicolas Thierry-Mieg Pierre F Ray Emmanuel Dulioust Marjorie Whitfield Aminata Tour é Source Type: research